Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 × 10−7; empirical p < 1 × 10−5; λS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 × 10−5; empirical p < 1 × 10−4; λS = 2.3) that were Y chromosome–lineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease.

The recombinant surface protein of Theileria annulata (TaSP) was used in the standardization and validation of an enzyme linked immunosorbent assay (ELISA) for the detection of circulating antibodies against tropical theileriosis. ELISA data were expressed as the percentage positivity (PP) of the reactivity of an internal positive control. A total of 50 sera samples from a disease-free area were used for the calculation of the cut-off value which served as a threshold between the positive and the negative sera samples. This was determined as the mean PP plus two standard deviations or the twice the mean PP of the results obtained with these negative samples. The obtained thresholds were 17.8% and 18.3%, respectively. Accordingly, the reactivity of 140 field sera samples collected at random from an area known to be endemic for tropical theileriosis in Sudan was determined as PP values which were then compared to the results obtained using the indirect fluorescence antibody test (IFAT) from the same samples. Both tests showed a high degree of correlation. The TaSP-ELISA had a sensitivity of 99.1% and specificity of 90.47% when taking the IFAT as a reference test. Our test has proved its suitability for the diagnosis of tropical theileriosis and could be used in serological surveys to map out the prevalence of the disease or to monitor vaccination efficiencies in disease-free populations.

An ELISA based on a recombinant Theileria annulata surface protein (TaSP) was evaluated for detection of antibodies in sera from cattle exposed to tropical theileriosis in Sudan. The reference positive samples, used in this study, were from Theileria-infected populations and consisted of 80 cattle from an endemic area in Khartoum State, with high antibody titers in the indirect fluorescent antibody test (IFAT). The reference negative samples were taken from non-exposed populations and consisted of 120 cattle maintained under strict tick control at a commercial farm in Sudan. The cut-off value determined by Two-Graph Receiver-Operating Characteristic (TG-ROC) curves was set at 31.6%, based on the positive reference samples. Further diagnostic validation was performed, which consisted of the measurement of the area under the ROC (AUC) and by valid range proportion (VRP), which was 0.97 and 0.98 for the cut-off, respectively. There were no cross-reactions with antibodies raised against Babesia spp. It is concluded that the TaSP ELISA is a useful test for the diagnosis of T. annulata infection in cattle under field conditions.

DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated as the chromosome 6q27 VL susceptibility gene.